140 research outputs found

    Political and Cognitive Structures Underlying Scientific Inquiry in the University: The Challenge to Educational Researchers

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    There is a disabling avalanche of scientific production which has overtaken most students of the behavioral sciences. Though science is advanced by this production, much of it is seen to be of marginal value. This has caused some disenchantment among university students with psychology-based research. To understand the sources of this problem, several phenomena are re-examined: (a) the functional autonomy of research paradigms and their assumptive justifica- tions, (b) the failure to discard them when their dysfunction interferes with inquiry directed to solving pressing social problems, and (c) the intersection of politics, academic policies, and the reward structures woven into publication and research networks. The challenge to university researchers, among others, that these conditions impose, are assessed, and suggestions for countering them are presented.L'hypertrophie de la production scientifique dans les sciences du comportement semble avoir créé un climat de désenchantement et d'inutilité par rapport à la recherche. Pour comprendre cette situation, les phénomÚnes suivants sont analysés: (a) l'autonomie fonctionelle et les postulats explicatifs des schemes de recherche, (b) la résistance et la durabilité des modÚles de recherche, (c) les contraintes politiques et socio-économiques de la recherche et de la publication. Les implications de cette situation en particulier dans les milieux académiques sont abordées. Des propositions et des suggestions susceptibles d'améliorer un développement fidÚle et valide de la recherche sont présentées

    Rotary quern and millstone roughouts beyond their quarries

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    Anderson, T.J., Alonso, N. (eds), Tilting at Mills: The Archaeology and Geology of Mills and Milling. Revista d’Arqueologia de Ponent. NĂșmero Extra 4, 2019. ISBN: 9788491440291Groups of unfinished quern and millstones (roughouts) have been recovered in Western Europe in the sea, in rivers and along ancient roads. They have also been unearthed during archaeological excavations of cities and rural sites. These different assemblages share similarities: the grinding surfaces are not finished, the eyes are rarely pierced and the handle holes are not cut. These groups evidence a segmentation of the operational sequence of production in Antiquity, from block extraction to their sale, with the transport of unfinished products and final shaping taking place in workshops beyond the quarry near their place of use. This model differs from that in the Middle Ages where millstones were transported in a finished form

    Snow spectral albedo at Summit, Greenland: measurements and numerical simulations based on physical and chemical properties of the snowpack

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    The broadband albedo of surface snow is determined both by the near-surface profile of the physical and chemical properties of the snowpack and by the spectral and angular characteristics of the incident solar radiation. Simultaneous measurements of the physical and chemical properties of snow were carried out at Summit Camp, Greenland (72°36® N, 38°25® W, 3210 m a.s.l.) in May and June 2011, along with spectral albedo measurements. One of the main objectives of the field campaign was to test our ability to predict snow spectral albedo by comparing the measured albedo to the albedo calculated with a radiative transfer model, using measured snow physical and chemical properties. To achieve this goal, we made daily measurements of the snow spectral albedo in the range 350–2200 nm and recorded snow stratigraphic information down to roughly 80 cm. The snow specific surface area (SSA) was measured using the DUFISSS instrument (DUal Frequency Integrating Sphere for Snow SSA measurement, Gallet et al., 2009). Samples were also collected for chemical analyses including black carbon (BC) and dust, to evaluate the impact of light absorbing particulate matter in snow. This is one of the most comprehensive albedo-related data sets combining chemical analysis, snow physical properties and spectral albedo measurements obtained in a polar environment. The surface albedo was calculated from density, SSA, BC and dust profiles using the DISORT model (DIScrete Ordinate Radiative Transfer, Stamnes et al., 1988) and compared to the measured values. Results indicate that the energy absorbed by the snowpack through the whole spectrum considered can be inferred within 1.10%. This accuracy is only slightly better than that which can be obtained considering pure snow, meaning that the impact of impurities on the snow albedo is small at Summit. In the near infrared, minor deviations in albedo up to 0.014 can be due to the accuracy of radiation and SSA measurements and to the surface roughness, whereas deviations up to 0.05 can be explained by the spatial heterogeneity of the snowpack at small scales, the assumption of spherical snow grains made for DISORT simulations and the vertical resolution of measurements of surface layer physical properties. At 1430 and around 1800 nm the discrepancies are larger and independent of the snow properties; we propose that they are due to errors in the ice refractive index at these wavelengths. This work contributes to the development of physically based albedo schemes in detailed snowpack models, and to the improvement of retrieval algorithms for estimating snow properties from remote sensing data

    Combined hepatocellular-cholangiocarcinomas exhibit progenitor features and activation of Wnt and TGFÎČ signaling pathways

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    Intrahepatic malignant tumours include hepatocellular carcinomas (HCC), cholangiocarcinomas (CC) and combined hepatocholangiocarcinomas (cHCC-CC), a group of rare and poorly characterized tumours that exhibit both biliary and hepatocytic differentiation. The aim of the study was to characterize the molecular pathways specifically associated with cHCC-CC pathogenesis. We performed a genome-wide transcriptional analysis of 20 histologically defined cHCC-CC and compared them with a series of typical HCC and of CC. Data were analysed by gene set enrichment and integrative genomics and results were further validated in situ by tissue microarray using an independent series of 152 tumours. We report that cHCC-CC exhibit stem/progenitor features, a down-regulation of the hepatocyte differentiation program and a commitment to the biliary lineage. TGFÎČ and Wnt/ÎČ-catenin were identified as the two major signalling pathways activated in cHCC-CC. A ÎČ-catenin signature distinct from that observed in well-differentiated HCC with mutant ÎČ-catenin was found in cHCC-CC. This signature was associated with microenvironment remodelling and TGFÎČ activation. Furthermore, integrative genomics revealed that cHCC-CC share characteristics of poorly differentiated HCC with stem cell traits and poor prognosis. The common traits displayed by CC, cHCC-CC and some HCC suggest that these tumours could originate from stem/progenitor cell(s) and raised the hypothesis of a potential continuum between intrahepatic CC, cHCC-CC and poorly differentiated HC

    Impact of Low Flow on the Outcome of High-Risk Patients Undergoing Transcatheter Aortic Valve Replacement

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    ObjectivesThis study sought to assess the impact of baseline left ventricular (LV) outflow, LV ejection fraction (LVEF), and transvalvular gradient on outcomes following transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis (AS).BackgroundLow flow (i.e., reduced stroke volume index [SVi]) can occur with both reduced and preserved LVEF. Low flow is often associated with low gradient despite severe stenosis and with worse outcomes following surgical aortic valve replacement. However, there are few data about the impact of low flow on outcomes following TAVR.MethodsWe retrospectively analyzed the clinical, Doppler-echocardiographic, and outcome data prospectively collected in 639 patients who underwent TAVR for symptomatic severe AS in 2 Canadian centers.ResultsIn this cohort, 334 (52.3%) patients had a low flow (SVi <35 ml/m2) and these patients had increased 30-day mortality (11.4 vs. 5.9%, p = 0.01), 2-year all-cause mortality (35.3 vs. 30.9%, p = 0.005), and 2-year cardiovascular mortality (25.7 vs. 16.8%, p = 0.01) compared with patients with normal flow. Reduced flow was an independent predictor of 30-day mortality (odds ratio: 1.94, p = 0.026), cumulative all-cause mortality (hazard ratio: 1.27 per 10 ml/mÂČ SVi decrease, p = 0.016), and cumulative cardiovascular mortality (hazard ratio: 1.29 per 10 ml/mÂČ decrease, p = 0.04). Despite significant association in univariable analyses, low LVEF and low mean gradient were not found to be independent predictors of outcomes in multivariable analyses.ConclusionsLow flow but not low LVEF or low gradient is an independent predictor of early and late mortality following TAVR in high-risk patients with severe AS. SVi should be integrated in the risk stratification process of these patients

    Interleukin-18 produced by bone marrow- derived stromal cells supports T-cell acute leukaemia progression

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    International audienceDevelopment of novel therapies is critical for T-cell acute leukae-mia (T-ALL). Here, we investigated the effect of inhibiting the MAPK/MEK/ERK pathway on T-ALL cell growth. Unexpectedly, MEK inhibitors (MEKi) enhanced growth of 70% of human T-ALL cell samples cultured on stromal cells independently of NOTCH activa-tion and maintained their ability to propagate in vivo. Similar results were obtained when T-ALL cells were cultured with ERK1/ 2-knockdown stromal cells or with conditioned medium from MEKi-treated stromal cells. Microarray analysis identified interleu-kin 18 (IL-18) as transcriptionally up-regulated in MEKi-treated MS5 cells. Recombinant IL-18 promoted T-ALL growth in vitro, whereas the loss of function of IL-18 receptor in T-ALL blast cells decreased blast proliferation in vitro and in NSG mice. The NFKB pathway that is downstream to IL-18R was activated by IL-18 in blast cells. IL-18 circulating levels were increased in T-ALL-xeno-grafted mice and also in T-ALL patients in comparison with controls. This study uncovers a novel role of the pro-inflammatory cytokine IL-18 and outlines the microenvironment involvement in human T-ALL development

    Myocardial injury following transcatheter aortic valve implantation : insights from delayed-enhancement cardiovascular magnetic resonance

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    Aims: The aim of this study was to evaluate the presence, localisation and extent of myocardial injury as determined by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: A total of 37 patients, who underwent successful TAVI with a balloon-expandable valve (transapical [TA], n=11; non-TA, n=26), were included. Cardiac biomarker (CK-MB and cTnT) lev- els were determined at baseline and following TAVI. CMR was performed within a week before and within 30 days following TAVI. Some increase in cardiac biomarkers was detected in 97% of the patients as deter- mined by a rise in cTnT, and in 49% of the patients as determined by a rise in CK-MB. Following TAVI, no new myocardial necrosis defects were observed with the non-TA approach. Nonetheless, all patients who underwent TAVI through the TA approach had new focal myocardial necrosis in the apex, with a median myo-cardial extent and necrotic mass of 5% [2.0-7.0] and 3.5 g [2.3-4.5], respectively. Conclusions: Although some increase in cardiac biomarkers of myocardial injury was systematically detected following TAVI, new myocardial necrosis as evaluated by CMR was observed only in patients undergoing the procedure through the TA approach, involving ~5% of the myocardium in the apex

    Green Edge ice camp campaigns : understanding the processes controlling the under-ice Arctic phytoplankton spring bloom

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    The Green Edge initiative was developed to investigate the processes controlling the primary productivity and fate of organic matter produced during the Arctic phytoplankton spring bloom (PSB) and to determine its role in the ecosystem. Two field campaigns were conducted in 2015 and 2016 at an ice camp located on landfast sea ice southeast of Qikiqtarjuaq Island in Baffin Bay (67.4797∘ N, 63.7895∘ W). During both expeditions, a large suite of physical, chemical and biological variables was measured beneath a consolidated sea-ice cover from the surface to the bottom (at 360 m depth) to better understand the factors driving the PSB. Key variables, such as conservative temperature, absolute salinity, radiance, irradiance, nutrient concentrations, chlorophyll a concentration, bacteria, phytoplankton and zooplankton abundance and taxonomy, and carbon stocks and fluxes were routinely measured at the ice camp. Meteorological and snow-relevant variables were also monitored. Here, we present the results of a joint effort to tidy and standardize the collected datasets, which will facilitate their reuse in other Arctic studies

    Unravelling the sex-specific diversity and functions of adrenal gland macrophages

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    Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.</p

    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

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    Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors
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